Research Articles (Medical Microbiology)

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Missed rifampicin and isoniazid resistance by commercial molecular assays
(South African Medical Association, 2024-07) Richards, L.; Ismail, Farzana; Nel, J.; Omar, Shaheed Vally
Drug-resistant tuberculosis (TB) has poor outcomes unless resistance is detected early, ideally by commercially available molecular tests. We present a case of occult multidrug-resistant TB where both rifampicin and isoniazid resistance were missed by molecular testing and were only identified by phenotypic testing.
Innovative timing strategies for tuberculosis household contact investigation : cost-effectiveness analysis from a randomized trial in rural and urban South Africa (Kharituwe Study)
(Elsevier, 2025-06) Young, Neenah; Biché, Patrick; Mohlamonyane, Mbali; Morolo, Matshidiso; Maholwana, Babalwa; Ahmed, Khatija; Martinson, Neil; Hanrahan, Colleen F.; Dowdy, David W.
BACKGROUND : Household contact investigation (HCI) for tuberculosis (TB) is recommended but often limited by resource constraints, particularly for individuals unavailable during business hours. METHODS : We conducted an economic evaluation from January 1, 2022, through December 31, 2022, nested within a randomized trial in South Africa (“Kharituwe”) comparing standard HCI for TB and two novel strategies: HCI during holiday periods in a rural setting and off-peak HCI during weekends and evenings in an urban setting. Costs were derived from 2022 expenditures, and secondary TB cases were defined by positive sputum cultures. As a secondary outcome of the Kharituwe Study, we assessed the incremental cost-effectiveness ratio (ICER) of each strategy against a hypothetical no-HCI scenario from the health system perspective in 2022 US dollars. Cost-effectiveness was assessed using a country-specific willingness-to-pay threshold of US$3015 per disability-adjusted life year (DALY) averted. The trial is registered with clincaltrials.gov (NCT04520113). FINDINGS : Relative to a hypothetical no-HCI approach, standard HCI was estimated to cost US$1400 [95% uncertainty interval (UI): $1000–$2100] per DALY averted in the urban setting and US$3600 [95% UI: $2500–$5400] in the rural setting. Corresponding cost-effectiveness ratios were US$1900 [95% UI: $1300–$2800] for off-peak (urban) and US$6400 [$3900–$10,000] for holiday-based (rural) HCI. Personnel costs, travel costs (in the rural setting), and TB prevalence among contact persons were primary drivers of cost-effectiveness. INTERPRETATION : HCI for TB is likely cost-effective in urban South Africa and may be cost-effective in rural settings, which face barriers including long travel times and lower TB prevalence. Holiday-based HCI was not found to be cost-effective. Integrating HCI for TB into broader home-based interventions may improve cost-effectiveness.
Expediting pathogen genomics adoption for enhanced foodborne disease surveillance in Africa
(Elsevier, 2025-01) Kanzi, Aquillah M.; Smith, Stella I.; Msefula, Chisomo; Mwaba, John; Ajayi, Abraham; Kwenda, Geoffrey; Tanui, Collins K.; Smith, Anthony Marius; Bester, Linda A.; Derra, Firehiwot A.; Yamba, Kaunda; Banda, Daniel L.; Kalule, John B.; Kumburu, Happiness H.; Fakim, Yasmina J.; Sithole, Nyasha; Njage, Patrick M.K.; Chikuse, Francis F.; Ondoa, Pascale; Tessema, Sofonias K.; Foster-Nyarko, Ebenezer
The role of genomics in public health surveillance has been accentuated by its crucial contributions during the COVID-19 pandemic, demonstrating its potential in addressing global disease outbreaks. While Africa has made strides in expanding multi-pathogen genomic surveillance, the integration into foodborne disease (FBD) surveillance remains nascent. Here we highlight the critical components to strengthen and scale-up the integration of whole genome sequencing (WGS) in foodborne disease surveillance across the continent. We discuss priority use-cases for FBD, and strategies for the implementation. We also highlight the major challenges such as data management, policy and regulatory frameworks, stakeholder engagement, the need for multidisciplinary collaborations and the importance of robust monitoring and evaluation, aiming to bolster Africa's preparedness and response to future health threats.
Prevalence of genes encoding carbapenem-resistance in Klebsiella pneumoniae recovered from clinical samples in Africa : systematic review and meta-analysis
(BioMed Central, 2025-04) Sisay, Assefa; Kumie, Getinet; Gashaw, Yalewayker; Nigatie, Marye; Gebray, Habtamu Mesele; Reta, Melese Abate
Please read abstract in the article.
Prevalence of colistin-resistant Enterobacteriaceae isolated from clinical samples in Africa: a systematic review and meta-analysis
(BioMed Central, 2025-03) Gashaw, Yalewayker; Asmare, Zelalem; Tigabie, Mitkie; Sisay, Asefa; Getatachew, Ermias; Tadesse, Selamyhun; Bitew, Getachew; Ashagre, Agenagnew; Misganaw, Tadesse; Gashaw, Muluken; Kassahun, Woldeteklehaymanot; Dejazimach, Zelalem; Jemal, Abdu; Gedfie, Solomon; Kumie, Getinet; Nigatie, Marye; Gelaw, Baye; Abebe, Wagaw; Kidie,Atitegeb Abera; Abate, Biruk Beletew; Reta, Melese Abate; Gelaw, Baye
BACKGROUND : Antimicrobial resistance among Enterobacteriaceae poses a significant global threat, particularly in developing countries. Colistin, a critical last-resort treatment for infections caused by carbapenem-resistant and multidrug-resistant strains, is increasingly facing resistance due to inappropriate use of colistin and the spread of plasmid-mediated resistance genes. Despite the significance of this issue, comprehensive and updated data on colistin resistance in Africa is lacking. Thus, the current study was aimed to determine the pooled prevalence of colistin-resistant Enterobacteriaceae in Africa. METHODS : A systematic search was conducted across PubMed, Scopus, ScienceDirect, and Google Scholar to identify relevant studies. Forty-one studies reporting on the prevalence of colistin resistance in Enterobacteriaceae isolates from clinical specimens in Africa were included in the analysis. Stata 17 software was used to calculate the pooled prevalence of colistin resistance, employing a random-effects model to determine the event rate of resistance. Heterogeneity across studies was assessed using the I2 statistic, and publication bias was evaluated using Egger’s test. Subgroup analyses were performed to address any identified heterogeneity. RESULTS : This systematic review analyzed the colistin resistance profile of 9,636 Enterobacteriaceae isolates. The overall pooled prevalence of colistin resistance was 26.74% (95% CI: 16.68–36.80). Subgroup analysis by country revealed significant variability in resistance rates, ranging from 0.5% in Djibouti to 50.95% in South Africa. Species-specific prevalence of colistin resistance was as follows: K. pneumoniae 28.8% (95% CI: 16.64%-41.05%), E. coli 24.5% (95% CI: 11.68%-37.3%), Proteus spp. 50.0% (95% CI: 6.0%-106.03%), and Enterobacter spp. 1.22% (95% CI: -0.5%-3.03%). Analysis based on AST methods revealed significant differences in colistin resistance rates (p = 0.001). The resistance rates varied between 12.60% for the disk diffusion method and 28.0% for the broth microdilution method. Additionally, a subgroup analysis of clinical specimens showed significant variation (p < 0.001) in colistin resistance. Stool specimen isolates had the highest resistance rate at 42.0%, while blood specimen isolates had a much lower resistance rate of 3.58%. CONCLUSIONS : Colistin resistance in Enterobacteriaceae is notably high in Africa, with significant variation across countries. This underscores the urgent need for effective antimicrobial stewardship, improved surveillance, and the development of new antibiotics.
Antimicrobial resistance pattern of Acinetobacter baumannii clinical isolate in Ethiopia. A systematic review and meta-analysis
(BioMed Central, 2025-04) Asmare, Zelalem; Tamrat, Ephrem; Erkihun, Mulat; Endalamaw, Kirubel; Alelign, Dagninet; Getie, Molla; Sisay, Assefa; Gashaw, Yalewayker; Reta, Melese Abate
BACKGROUND : Antimicrobial resistance (AMR) is a growing global health threat. Acinetobacter baumannii (A. baumannii) emerged as one of the most concerning critical priority pathogens due to its ability to develop resistance to multiple antimicrobial agents. In Ethiopia, the public health impact of AMR is increasingly significant, with A. baumannii responsible for a variety of infections. Although A. baumannii causes a range of infections in Ethiopian patients, the drug resistance status of the clinical isolates has not been thoroughly assessed. Therefore, this systematic review and meta-analysis aimed to determine the country-wide AMR of A. baumannii. METHODS : This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a search of articles on PubMed, Web of Science, Science Direct, Scopes electronic databases, Google Scholar search engine, and institutional repositories/libraries for studies published between 2015 and 2024. Eligible studies on A. baumannii-related infections and AMR in Ethiopia were assessed for quality using the Joanna Briggs Institute (JBI) criteria. Data on study characteristics were extracted, and statistical analyses, including heterogeneity (Invers of variance), publication bias (Eggers test), and subgroup analyses, were performed using STATA 17.0. A random effect model was used to compute the pooled prevalence of AMR. RESULTS : This systematic review and meta-analysis of 26 Ethiopian studies (26,539 participants) found an A. baumannii prevalence of 3.99% (95% CI: 3.01–4.98%) and 9.13% of all bacterial infections (95% CI: 6.73–11.54%). The most common infections were surgical site infections, urinary tract infections, pneumonia, and sepsis. Pooled resistance to antibiotics varied, with amikacin showing the lowest resistance (20.27%) (95% CI: 11.51–29.03) and cefotaxime the highest (83.18) (95% CI: 71.87–94.48). A pooled multi-drug resistant (MDR) A. baumannii was found in 88.22% (95% CI: 82.28–94.15) of isolates, with regional and infection-type variations, particularly in higher prevalence in Oromia and Amhara regions and sepsis cases. CONCLUSION : This systematic review underscores the alarming rise of antimicrobial resistance in A. baumannii, particularly against carbapenems. The findings highlight a high prevalence of MDR A. baumannii and widespread extended-spectrum beta-lactamase production, with notable regional variations in resistance patterns. These high resistance rates reinforce A. baumannii as a critical global health threat, necessitating urgent interventions such as enhanced antimicrobial stewardship programs, improved infection control measures, and the development of alternative treatment strategies. Healthcare professionals, policymakers, and researchers must collaborate to mitigate the clinical and public health impact of this pathogen. PROTOCOL REGISTRATION : This systematic review and meta-analysis was registered on PROSPERO (Registration ID: CRD42024623927).
Does a waiting room increase same-day treatment for sexually transmitted infections among pregnant women? A quality improvement study at South African primary healthcare facilities
(BioMed Central, 2025-04) Gigi, Ranjana M.S.; Mdingi, Mandisa M.; Butikofer, Lukas; Babalola, Chibuzor M.; Klausner, Jeffrey D.; Medina-Marino, Andrew; Muzny, Christina A.; Taylor, Christopher M.; Van de Wijgert, Janneke H.H.M.; Peters, Remco P.H.; Low, Nicola
BACKGROUND : Same-day testing and treatment of curable sexually transmitted infections (STI) is a strategy to reduce infection duration and onward transmission. South African primary healthcare facilities often lack sufficient waiting spaces. This study aimed to assess the proportion of, and factors influencing, pregnant women waiting for on-site STI test results before and after the installation of clinic-based waiting rooms. METHODS : We conducted an observational quality improvement study at 5 public primary healthcare facilities in South Africa from March 2021 to May 2023. The intervention was the installation of a waiting room in two clinics. Three clinics were used as comparators: two already had a waiting room in an existing building and one had access to a shared waiting area. The outcome was the percentage of women who waited for their STI test results. We conducted univariable and multivariable analyses and report marginal risk differences (with 95% confidence intervals, CI) of the proportions of women who waited for results. A subset of women answered structured questions about factors influencing their decision to wait for results. RESULTS : We analysed data from 624 women across the 5 facilities. Overall, 36% (95% CI 31 to 40) waited for their test results (range 7 to 89%). In the two intervention clinics, 17% (95% CI 11 to 24) waited for results before the introduction of a waiting room and 10% (95% CI 5 to 18) after (crude absolute difference − 7% (95% CI -16 to + 3), adjusted difference, -6% (95% CI -17 to + 5)). The percentages of pregnant women waiting for STI test results were higher throughout the study period in 2 clinics which always had a dedicated waiting room than in 2 clinics where a waiting room was installed, or in 1 clinic, which only had access to a shared waiting area. Most women reported before testing that they did not intend to wait and none of the suggested factors would change their decision. CONCLUSIONS : Introduction of a waiting room did not increase the proportion of women who waited for their results in this observational study. Future studies should investigate infrastructure, individual and test-based factors that affect same-day STI testing and treatment.
Twice-yearly Lenacapavir or daily F/TAF for HIV prevention in cisgender women
(Massachusetts Medical Society, 2024-10) Bekker, Linda-Gail; Das, Moupali; Karim, Quarraisha Abdool; Ahmed, Khatija; Batting, Joanne; Brumskine, William; Gill, Katherine; Harkoo, Ishana; Jaggernath, Manjeetha; Kigozi, Godfrey; Kiwanuka, Noah; Kotze, Philip; Lebina, Limakatso; Louw, Cheryl E.; Malahleha, Moelo; Manentsa, Mmatsie; Mansoor, Leila E.; Moodley, Dhayendre; Naicker, Vimla; Naidoo, Logashvari; Naidoo, Megeshinee; Nair, Gonasagrie; Ndlovu, Nkosiphile; Palanee-Phillips, Thesla; Panchia, Ravindre; Pillay, Saresha; Potloane, Disebo; Selepe, Pearl; Singh, Nishanta; Singh, Yashna; Spooner, Elizabeth; Ward, Amy M.; Zwane, Zwelethu; Ebrahimi, Ramin; Zhao, Yang; Kintu, Alexander; Deaton, Chris; Carter, Christoph C.; Baeten, Jared M.; Kiweewa, Flavia Matovu
BACKGROUND : There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women. METHODS : We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo. We assessed the efficacy of lenacapavir and F/TAF by comparing the incidence of HIV infection with the estimated background incidence in the screened population and evaluated relative efficacy as compared with F/TDF. RESULTS : Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74). Background HIV incidence in the screened population (8094 participants) was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio, 0.84; 95% CI, 0.55 to 1.28; P=0.21), and no evidence of a meaningful difference in HIV incidence was observed between F/TAF and F/TDF (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). Adherence to F/TAF and F/TDF was low. No safety concerns were found. Injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.9%); 4 participants in the lenacapavir group (0.2%) discontinued the trial regimen owing to injection-site reactions. CONCLUSIONS : No participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF.
Prevalence of antimalaria drug resistance-conferring mutations associated with sulphadoxine-pyrimethamineine-resistant Plasmodium falciparum in East Africa : a systematic review and meta-analysis
(BioMed Central, 2025-04) Abebe, Wagaw; Ashagre, Agenagnew; Misganaw, Tadesse; Dejazmach, Zelalem; Kumie, Getinet; Nigatie, Marye; Jemal, Abdu; Asmare, Zelalem; Kassahun, Woldeteklehaymanot; Gedfie, Solomon; Getachew, Ermias; Gashaw, Muluken; Ayana, Sisay; Gashaw, Yalewayker; Sisay, Assefa; Tadesse, Selamyhun; Eshetu, Tegegne; Awoke, Mulat; Kassanew, Birhanu; Kidie, Atitegeb Abera; Abate, Biruk Beletew; Reta, Melese Abate
BACKGROUND : The emergence and spread of drug resistance to antimalarial drugs pose a severe threat to effective malaria control and treatment. Although sulfadoxine-pyrimethamine resistance is well-documented, it is still the drug of choice for treating intermittent resistance. Molecular markers play a crucial role in tracking and understanding the prevalence of antimalarial drug resistance. Currently, there is insufficient information on the prevalence of molecular markers associated with sulfadoxine-pyrimethamine resistance in P. falciparum. OBJECTIVE : This systematic review and meta-analysis aimed to determine the pooled prevalence of antimalaria drug resistance-conferring markers associated with sulphadoxine-pyrimethamineine in Plasmodium falciparum in East Africa. METHODS : Systematic searches was performed to retrieve articles from PubMed, Scopus, Science Direct databases, and Google Scholar search engine. Sixteen potential studies that provided important data on markers for sulphadoxine-pyrimethamineine resistance in Plasmodium falciparum were systematically reviewed and analyzed. Nine antimalarial drug resistance markers responsible for sulphadoxine-pyrimethamineine resistance in Plasmodium falciparum were extracted separately into Microsoft Excel and analyzed using STATA 17.0. The inverse of variance was done to evaluate heterogeneity across studies. A funnel plot was used to determine the presence of publication bias. A trim-and-fill-meta-analysis was carried out to generate a bias-adjusted effect estimate. A random effect model was used to determine the pooled prevalence of markers responsible for sulphadoxine-pyrimethamineine resistance. Subgroup analysis was performed based on country and year of publication. RESULTS : A total of 16 studies were included for this systematic review and meta-analysis.The molecular markers like dhfr (N51I, C59R, S108N, 108N, 59R, and I164L), and dhps (A437G, K540E, & 540E) were selected for meta-analysis. From this meta-analysis, the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhfr 108N, dhfr 59R, and dhfr I164L was 88.6%, 85.3%, 89.6%, 92.2%, 71.5%, and 3.9%, respectively. Likewise, the aggregated prevalence of dhps A437G, dhps K540E, and dhps 540E was 90.2%, 80.9%, and 91.5%, respectively. The subgroup analysis based on year of publication showed that the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhps A437G, and dhps K540E, in studies conducted 2014–2018 was 97.11%, 90.57%, 96.45%, 90.89%, and 89.45%, respectively, while it was 82.03%, 81.78%, 85.12%, 89.24%, and 73.98%, respectively, in studies conducted 2019–2023. On the other hand, country-based analysis showed that the pooled prevalence of dhfr N51I, dhfr C59R, dhfr S108N, dhps A437G, and dhps K540E, in Kenya was 85.88%, 84.02%, 86.56%, 90.7%, and 77.55%, respectively. CONCLUSIONS : This systematic review and meta-analysis reveal a high prevalence of drug resistance markers associated with sulphadoxine-pyrimethamine resistance in Plasmodium falciparum across the East African region. This underscores the significant challenges in managing malaria infections caused by Plasmodium falciparum in the region. Therefore, regular monitoring, identification, and limiting of drug-resistance markers and drug-resistant P. falciparum strains must be sustained to ensure the effectiveness of malaria treatment.
Antimicrobial resistance profile of Pseudomonas aeruginosa clinical isolates from healthcare-associated infections in Ethiopia : a systematic review and meta-analysis
(Public Library of Science, 2024-08-13) Asmare, Zelalem; Reta, Melese Abate; Gashaw, Yalewayker; Sisay, Assefa; Gashaw, Muluken; Tamrat, Ephrem; Abebe, Wagaw; Misganaw, Tadesse; Ashagre, Agenagnew; Dejazmach, Zelalem; Kumie, Getinet; Nigatie, Marye; Ayana, Sisay; Jemal, Abdu; Gedfie, Solomon; Kassahun, Woldeteklehaymanot; Kassa, Mulat Awoke; Tadesse, Selamyhun; Abate, Biruk Beletew
BACKGROUND : Antimicrobial-resistant (AMR) bacterial infection is a significant global threat to the healthcare systems. Pseudomonas aeruginosa, the leading infectious agent in the healthcare setting is now one of the major threats due to AMR. A comprehensive understanding of the magnitude of AMR, particularly highly public health important pathogens such as P. aeruginosa, is necessary for the management of infections based on local information. OBJECTIVE : This systematic review and meta-analysis aimed to determine the country-wide AMR of P. aeruginosa. METHODS : Systematic searches were performed to retrieve articles from PubMed, Scopus, Web of Science, ScienceDirect electronic databases, Google Scholar search engine, and repository registrars from 2015 to 31st December 2023. Twenty-three studies that provided important data on AMR in P. aeruginosa were systematically reviewed and analyzed to determine the country-wide magnitude of P. aeruginosa AMR profile from healthcare-associated infections. AMR of P. aeruginosa to 10 different antibiotics were extracted separately into Microsoft Excel and analyzed using STATA 17.0. Cohen’s kappa was computed to determine the agreement between reviewers, the Inverse of variance (I2) was used to evaluate heterogeneity across studies, and Egger’s test to identify publication bias. A random effect model was used to determine the pooled resistance to each antibiotic. Subgroup analysis was performed by infection type and year of publication. RESULTS : This systematic review and meta-analysis revealed that the pooled prevalence of P. aeruginosa in clinical specimens associated with HAI was 4.38%(95%CI: 3.00–5.76). The pooled prevalence of AMR in P. aeruginosa for different antibiotics varies, ranging from 20.9% (95%CI: 6.2–35.8) for amikacin to 98.72% (95%CI: 96.39–101.4) for ceftriaxone. The pooled resistance was higher for ceftriaxone (98.72%), Trimethoprim-sulfamethoxazole (75.41), and amoxicillin-clavulanic acid (91.2). In contrast relatively lower AMR were observed for amikacin (20.9%) and meropenem (28.64%). The pooled multi-drug resistance (MDR) in P. aeruginosa was 80.5% (95%CI: 66.25–93.84). Upon subgroup analysis by infection types and year of publication, P. aeruginosa isolated from healthcare-associated infections exhibited higher resistance to ceftazidime (94.72%) compared to isolates from mixed types of healthcare-associated infections (70.84%) and surgical site infections (57.84%). Antimicrobial resistance in gentamicin was higher during the periods of 2018–2020 (73.96%), while comparatively lower during 2021–2023 (42.69%) and 2015–2017 (29.82%) CONCLUSIONS : Significantly high AMR and MDR were observed from this systematic review and meta-analysis. AMR obtained from this systematic review and meta-analysis urges the need for improved infection control, antimicrobial stewardship practices, and strengthened surveillance systems to control the spread of AMR and ensure effective treatment of P. aeruginosa infections.
Metagenomics analysis of sewage for surveillance of antimicrobial resistance in South Africa
(Public Library of Science, 2024-08-26) Smith, Anthony Marius; Ramudzulu, Masindi; Munk, Patrick; Avot, Baptiste J.P.; Esterhuyse, Kerneels C.M.; Van Blerk, Nico; KwendaI, Stanford; Sekwadi, Phuti
Our 24-month study used metagenomics to investigate antimicrobial resistance (AMR) abundance in raw sewage from wastewater treatment works (WWTWs) in two municipalities in Gauteng Province, South Africa. At the AMR class level, data showed similar trends at all WWTWs, showing that aminoglycoside, beta-lactam, sulfonamide and tetracycline resistance was most abundant. AMR abundance differences were shown between municipalities, where Tshwane Metropolitan Municipality (TMM) WWTWs showed overall higher abundance of AMR compared to Ekurhuleni Metropolitan Municipality (EMM) WWTWs. Also, within each municipality, there were differing trends in AMR abundance. Notably, within TMM, certain AMR classes (macrolides and macrolides_streptogramin B) were in higher abundance at a WWTW serving an urban high-income area, while other AMR classes (aminoglycosides) were in higher abundance at a WWTW serving a semi-urban low income area. At the AMR gene level, all WWTWs samples showed the most abundance for the sul1 gene (encoding sulfonamide resistance). Following this, the next 14 most abundant genes encoded resistance to sulfonamides, aminoglycosides, macrolides, tetracyclines and beta-lactams. Notably, within TMM, some macrolide-encoding resistance genes (mefC, msrE, mphG and mphE) were in highest abundance at a WWTW serving an urban high-income area; while sul1, sul2 and tetC genes were in highest abundance at a WWTW serving a semi-urban low income area. Differential abundance analysis of AMR genes at WWTWs, following stratification of data by season, showed some notable variance in six AMR genes, of which blaKPC-2 and blaKPC-34 genes showed the highest prevalence of seasonal abundance differences when comparing data within a WWTW. The general trend was to see higher abundances of AMR genes in colder seasons, when comparing seasonal data within a WWTW. Our study investigated wastewater samples in only one province of South Africa, from WWTWs located within close proximity to one another. We would require a more widespread investigation at WWTWs distributed across all regions/provinces of South Africa, in order to describe a more comprehensive profile of AMR abundance across the country.
Prevalence of pulmonary tuberculosis among key and vulnerable populations in hotspot settings of Ethiopia. A systematic review and meta-analysis
(Public Library of Science, 2024-08-29) Reta, Melese Abate; Asmare, Zelalem; Sisay, Assefa; Gashaw, Yalewayker; Getachew, Ermias; Gashaw, Muluken; Dejazmach, Zelalem; Jemal, Abdu; Gedfie, Solomon; Kumie, Getinet; Nigatie, Marye; Abebe, Wagaw; Ashagre, Agenagnew; Misganaw, Tadesse; Kassahun, Woldeteklehaymanot; Tadesse, Selamyhun; Geteneh, Alene; Kidie, Atitegeb Abera; Abate, Biruk Beletew; Maningi, Nontuthuko Excellent; Fourie, Petrus Bernardus
BACKGROUND : Despite the decline in tuberculosis (TB) incidence across many regions worldwide, including Ethiopia, the disease remains highly concentrated among vulnerable or socially marginalized populations and in high-risk settings. This systematic review and meta-analysis aims to estimate the pooled prevalence of pulmonary tuberculosis (PTB) among key and vulnerable populations (KVPs) residing in hotspot settings in Ethiopia. METHODS : Potential papers were searched systematically in PubMed, Scopus, ScienceDirect databases, Google Scholar search engine, and institutional electronic repositories/registrars. A total of 34 potential articles that provide necessary information on the prevalence of PTB were reviewed and data were analyzed to determine the pooled prevalence of PTB among KVPs. The relevant data were recorded and analyzed using STATA 17.0. Cohen’s kappa was computed to determine the agreement between reviewers, the Inverse of variance (I2) to evaluate heterogeneity across studies, and Egger’s test to identify publication bias. A random effect model was used to determine the pooled prevalence of PTB, subgroup analysis was computed by types of hotspot settings and year of publication. RESULTS : This meta-analysis demonstrates that the pooled prevalence of PTB among populations residing in hotspot settings in Ethiopia was 11.7% (95% confidence interval (95CI): 7.97–15.43) with an I2 of 99.91% and a p< 0.001. Furthermore, the subgroup analysis unveiled the pooled prevalence of PTB among KVPs residing in different hotspot settings as follows: Prison inmates 8.8% (95CI: 5.00–12.55%), University students 23.1% (95CI: 15.81–30.37%), Refugees 28.4% (95CI: -1.27–58.15%), Homeless peoples 5.8% (95CI: -0.67–12.35%), Healthcare settings 11.1% (95CI: 0.58–21.63%), Spiritual holy water sites attendees 12.3% (95CI: -6.26–30.80%), and other high-risk settings 4.3% (95CI: 0.47–8.09%). Besides, the subgroup analysis revealed that the pooled prevalence of PTB post-2015 was 10.79% (95CI: 5.94–15.64%), whereas it stood at 14.04% (95CI: 10.27–17.82%) before 2015. CONCLUSION : The prevalence of PTB among KVPs residing in the hotspot settings in Ethiopia remains significant, with a weighted pooled prevalence of 11.7%. Thus, the national TB control programs should give due attention and appropriate control measures should be instituted that include regular systematic TB screening, compulsory TB testing for presumptive TB cases among KVPs, and tightened infection control at hotspot settings.
Tuberculin skin test surveys and the annual risk of Tuberculous infection in school children in Northern KwaZulu-Natal
(Public Library of Science, 2024-06-18) Yates, Tom A.; Cebekhulu, Siphiwe; Mthethwa, Mumsy; Fourie, Petrus Bernardus; Newell, Marie-Louise; Abubakar, Ibrahim; Tanser, Frank
Tuberculin skin test surveys in primary school children can be used to quantify Mycobacterium tuberculosis transmission at community level. KwaZulu-Natal province, South Africa, is home to 11.5 million people and suffers a burden of tuberculosis disease that is among the highest in the world. The last tuberculin survey in the province was undertaken in 1979. We performed a tuberculin skin test survey nested within a demographic and health household surveillance programme in Northern KwaZulu-Natal. We enrolled children aged between six and eight years of age attending primary schools in this community. Mixture analysis was used to determine tuberculin skin test thresholds and the Annual Risk of Tuberculous Infection derived from age at testing and infection prevalence. The Community Infection Ratio, a measure of the relative importance of within-household and community transmission, was calculated from data on tuberculin positivity disaggregated by household tuberculosis contact. Between June and December 2013, we obtained tuberculin skin test results on 1240 children. Mixture analysis proved unstable, suggesting two potential thresholds for test positivity. Using a threshold of 10mm or treating all non zero reactions as positive yielded estimates of the Annual Risk of Tuberculous Infection of 1.7% (1.4–2.1%) or 2.4% (2.0–3.0%). Using the same thresholds and including children reported to be receiving TB treatment as cases, resulted in estimates of 2.0% (1.6–2.5%) or 2.7% (2.2–3.3%). The Community Infection Ratio was 0.58 (0.33–1.01). The force of infection in this community is lower than that observed in Western Cape province, South Africa, but higher than that observed in community settings in most other parts of the world. Children in this community are commonly infected with Mycobacterium tuberculosis outside the home. Interventions to interrupt transmission are urgently needed.
Human source severe acute respiratory syndrome coronavirus 2 aerosol transmission to remote sentinel hamsters
(Oxford University Press, 2025-04) Roy, Chad J.; Barer, Michael R.; Ueckermann, Veronica; Beddingfield, Brandon; Cordier, David; Fourie, Bernard P.; Vincent, Richard; Dibobo, Sego; VanReenen, Toby; Jensen, Paul; De Kock, Oliva; De Kock, Elsabe; Nardell, Edward
BACKGROUND : Bioaerosol-mediated transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via building ventilation systems has yet to be convincingly demonstrated. We used the South African Airborne Infections Research (AIR) facility near Pretoria to study human-to-animal (H2A) transmission of SARS-CoV-2 in newly diagnosed patients. While the facility was built to study tuberculosis transmission, this was its first adaptation to study H2A virus transmission. METHODS : Patients with clinically confirmed coronavirus disease 2019 were housed for up to 4 days in in the AIR facility with continuously exhausting patient ward air to hamsters housed in animal exposure rooms. After a 3-week exposure period, animals were held for an additional week to allow for antibody development. Animal sera were analyzed for anti-spike and plaque reduction activities and lung samples for pathology. RESULTS : Seven patients provided ≥400 in-residence hours over a 17-day period. Pair-housed naive golden Syrian hamsters (n = 216) received continuous exposure to mixed patient ward exhaust. Serum analyses revealed anti-SARS-CoV-2 immunoglobulin G in 58% of animals tested. Plaque reduction assays on 7 high-titer serum samples revealed neutralizing activity. CONCLUSIONS : These results support the concept that viral bioaerosols generated from patients remain infectious over long-distance transport through a building ventilation system. The seroconversion among sentinel animals supports the long-held belief that airborne infections manifest as a stochastic rather than deterministic event that is subject to a threshold dose effect. Further confirmatory studies are necessary to characterize the relationship between the bioaerosol delivered and the infections that result in this controlled H2A transmission model.
Xpert MTB/XDR implementation in South Africa : cost outcomes of centralised vs. decentralised approaches
(International Union Against Tuberculosis and Lung Disease, 2024-05-01) Cassim, N.; Omar, Shaheed Vally; Masuku, S.D.; Moultrie, H.; Stevens, W.S.; Ismail, Farzana; Da Silva, P.
INTRODUCTION : In South Africa, Xpert® MTB/RIF Ultra (Ultra) is the recommended diagnostic assay for TB with line-probe assays for first- (LPAfl) and second-line drugs (LPAsl) providing additional drug susceptibility testing (DST) for samples that were rifampicin-resistant (RR-TB). To guide implementation of the recently launched Xpert® MTB/XDR (MTB/XDR) assay, a cost-outcomes analysis was conducted comparing total costs for genotypic DST (gDST) for persons diagnosed with RR-TB considering three strategies: replacing LPAfl/LPAsl (centralised level) with MTB/XDR vs. Ultra reflex testing (decentralised level). Further, DST was performed using residual specimen following RR-TB diagnosis. METHODS : The total cost of gDST was determined for three strategies, considering loss to follow-up (LTFU), unsuccessful test rates, and specimen volume. RESULTS : For 2019, 9,415 persons were diagnosed with RR-TB. A 35% LTFU rate between RR-TB diagnosis and LPAfl/LPAsl-DST was estimated. Unsuccessful test rates of 37% and 23.3% were reported for LPAfl and LPAsl, respectively. The estimated total costs were $191,472 for the conventional strategy, $122,352 for the centralised strategy, and $126,838 for the decentralised strategy. However, it was found that sufficient residual volume for reflex MTB/XDR testing is a limiting factor at the decentralised level. CONCLUSION : Centralising the implementation of XDR testing, as compared to LPAfl/LPAsl, leads to significant cost savings.
Global prevalence, resistance rates, and underlying resistance mechanisms of clinical Mycoplasma and Ureaplasma species
(Oxford University Press, 2025-01) Ramaloko, Winnie Thabisa; Maningi, Nontuthuko Excellent; Osei Sekyere, John
Mycoplasmas are significant pathogens in human health, implicated in a range of clinical conditions from respiratory infections to urogenital disorders. Their resistance to commonly used antibiotics poses a substantial challenge to treatment and control. This study aims to provide a comprehensive overview of the global distribution of clinical mycoplasmas, elucidate their resistance to various antibiotics, and identify the genetic and molecular mechanisms underlying their resistance. A systematic review and meta-analysis were conducted, collating data from peer-reviewed publications between 2012 and 2024. The UK (100%) and Germany (98%) reported high numbers of respiratory mycoplasmas, with 7% and 2% being resistant to macrolides. For urogenital mycoplasmas, Iceland (99%) and Estonia (94%) reported a high prevalence of Mycoplasma species, whereas the UK (85%), France (82%), and the USA (82%) reported a high prevalence of Ureaplasma species. High resistance rates in Mycoplasma and Ureaplasma have been reported in Greenland (100%) and the UK (86%), respectively. The rising resistance rates in these species underscore an urgent need for updated treatment guidelines and the development of novel therapeutic options. Our findings highlight the importance of tailored antibiotic stewardship and the potential of genomic insights in guiding effective treatment strategies.
From pregnancy to beyond : renewed emphasis on comprehensive HIV prevention in South Africa
(Lippincott Williams and Wilkins, 2025-03) Babalola, Chibuzor M.; Peters, Remco P.H.; Muzny, Christina A.; Davey, Dvora Joseph; Taylor, Christopher M.; Mdingi, Mandisa M.; Mukomana, Freedom; De Vos, Lindsey; Medina‑Marino, Andrew; Klausner, Jeffrey D
South Africa continues to document high HIV prevalence, particularly among pregnant women, highlighting significant prevention gaps. This viewpoint triangulates findings from the Sixth South African HIV Prevalence Survey, the 2022 Antenatal HIV Sentinel Survey, and our ongoing “Philani Ndiphile” trial, which is evaluating STI screening algorithms to improve pregnancy outcomes. Despite a recent national decline in antenatal HIV prevalence, the Philani trial recorded an HIV prevalence of 28.6% among pregnant women, mirroring high rates across the Eastern Cape Province. The trial cohort also revealed a significant increasing trend in HIV prevalence with age, from 6% at 18 years to 63% at 43 years, highlighting the need for age-targeted interventions in young women of childbearing age. National progress toward UNAIDS’ targets for HIV status knowledge and ART initiation is evident; however, viral suppression remains a challenge, reflected in the 20% of Philani participants newly initiated or reinitiated on ART at their first antenatal visit. Efforts to reduce new HIV infections require strengthening, as high incidence rates persist among young women and during pregnancy and postpartum. Expanding access to oral and long-acting PrEP for pregnant and postpartum women is critical. Current coverage is low, and while new options show promise, implementation guidance remains limited. Socioeconomic factors, such as poverty and intimate partner violence, exacerbate HIV risk. Comprehensive interventions, including educational and vocational support, engaging male partners, and addressing STIs are essential. Continued support from global health partnerships and innovation in prevention strategies are vital to ending the epidemic and ensuring equitable outcomes.
Molecular epidemiology and AMR perspective of diarrhoeagenic Escherichia coli in Africa
(Springer, 2024-12) Kalule, John Bosco; Bester, Linda A.; Banda, Daniel L.; Derra, Firehiwot Abera; Msefula, Chisomo; Smith, Anthony Marius; Ajayi, Abraham; Kumburu, Happiness; Kwenda, Geoffrey; Yamba, Kaunda; Mwaba, John; Fakim, Yasmina J.; Sithole, Nyasha; Kanzi, Aquillah M.; Njage, Patrick M.K.; Chikuse, Francis; Tessema, Sofonias K.; Smith, Stella I.; Foster‑Nyarko, Ebenezer
INTRODUCTION : Diarrhoeagenic Escherichia coli (DEC) persistently challenges public health in Africa, contributing substantially to the diarrhoeal disease burden. This systematic review and meta-analysis illuminate the distribution and antimicrobial resistance (AMR) patterns of DEC pathotypes across the continent. METHODS : The review selectively focused on pathotype-specific studies reporting prevalence and/or AMR of human-derived DEC pathotypes from African nations, excluding data from extra-intestinal, animal, and environmental sources and studies focused on drug and mechanism experiments. Pertinent studies were retrieved from SCOPUS, PubMed, and EBSCOhost, processed with Covidence, and screened in alignment with PRISMA guidelines. RESULTS : The reviewed studies were predominantly hospital-based (80%) and paediatric-focused (91%), with a meagre 4.4% documenting DEC outbreaks. Seven DEC pathotypes were discerned, with Enteroaggregative E. coli (EAEC) being notably prevalent (43%, 95% CI 30–55%) and Entero-invasive E. coli (EIEC) least prevalent (24%, 95% CI 17–32%). Identified non-susceptibilities were noted against essential antibiotics including ciprofloxacin, ceftriaxone, and ampicillin, while instances of carbapenem and Extended-Spectrum ß-Lactamase (ESBL) resistance were scarce. CONCLUSION : Despite sporadic data on DEC prevalence and AMR in Africa, particularly in community settings, a palpable gap remains in real-time outbreak surveillance and comprehensive data documentation. Augmenting surveillance and embracing advancements in molecular/genomic characterisation techniques are crucial to precisely discerning DEC's actual impact and resistance continuum in Africa.
Detection of the epidemic Pseudomonas aeruginosa AUST-03 (ST242) strain in people with cystic fibrosis in South Africa
(Wiley, 2024-12) Hamiwe, Thabo; White, Debbie A.; Kwenda, Stanford; Ismail, Arshad; Klugman, Susan; Van Bruwaene, Lore; Goga, Ameena Ebrahim; Kock, Marleen M.; Smith, Anthony Marius; Ehlers, Marthie Magdaleen; marthie.ehlers@up.ac.za
INTRODUCTION: Pseudomonas aeruginosa AUST-03 (ST242) has been reported to cause epidemics in people with CF (pwCF) from Australia and has been associated with multidrug resistance and increased morbidity and mortality. Here, we report an epidemic P. aeruginosa (AUST-03) strain in South African pwCF detected at a public hospital and characterize the genomic antibiotic resistance determinants. METHODS: The P. aeruginosa AUST-03 (ST242) study isolates were analysed with whole genome sequencing using the Illumina NextSeq2000 platform. Raw sequencing reads were processed using the Jekesa pipeline and multilocus sequence typing and genomic antibiotic resistance characterization was performed using public databases. Genetic relatedness between the study isolates and global P. aeruginosa ST242 from public databases was determined using a maximum-likelihood phylogenetic tree. Antibiotic susceptibility testing was performed using the disk diffusion and broth microdilution techniques. RESULTS: A total of 11 P. aeruginosa AUST-03 isolates were isolated from two children with CF. The majority (8/11) of these isolates were multidrug-resistant (MDR) or extensively drug resistant; and the multidrug efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM were the most clinically relevant antibiotic resistance determinants and were detected in all of the isolates. The study isolates were the most closely related to a 2020 P. aeruginosa AUST-03 (ST242) CF isolate from Russia. CONCLUSION: Epidemic MDR P. aeruginosa strains are present at South African public CF clinics and need to be considered when implementing segregation and infection control strategies to prevent possible spread and outbreaks.
In vitro evaluation of the binding activity of novel mouse IgG1 opsonic monoclonal antibodies to Mycobacterium tuberculosis and other selected mycobacterial species
(Elsevier, 2024-05) Nyazema, Kudzai B.; Shey, Bong-Akee; Sei, Clara J.; Peters, Remco P.H.; Maningi, Nontuthuko Excellent; Fischer, Gerald W.; Fourie, Petrus Bernardus
Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of antibodies as adjunct therapeutic agents. This study assessed the binding efficacy of two novel IgG1 opsonic monoclonal antibodies (MABs; GG9 & JG7) at 5, 10, and 25 μg/mL to live cultures of Mycobacterium tuberculosis, M. avium, M. bovis, M. fortuitum, M. intracellulare, and M. smegmatis American Type Culture Collection laboratory reference strains, as well as clinical susceptible, multidrug resistant, and extensively drug resistant M. tuberculosis strains using indirect enzyme-linked immunosorbent assays. These three MAB concentrations were selected from a range of concentrations used in previous optimization (binding and functional) assays. Both MABs bound to all mycobacterial species and sub-types tested, albeit to varying degrees. Statistically significant differences in MAB binding activity were observed when comparing the highest and lowest MAB concentrations (p < 0.05) for both MABs GG9 and JG7, irrespective of the M. tuberculosis resistance profile. Binding affinity increased with an increase in MAB concentration, and optimal binding was observed at 25 μg/mL. JG7 showed better binding activity than GG9. Both MABs also bound to five MOTT species, albeit at varied levels. This non-selective binding to different mycobacterial species suggests a potential role for GG9 and JG7 as adjunctive agents in anti-TB chemotherapy with the aim to enhance bacterial killing.

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